Rituximab for Behçet's

While I think that (pasterized) milk, dairy and eggs are causing Behçet's, it is interesting to see that Rituximab seems to be helping Behçet's patients.

Rituximab in intractable ocular lesions of Behcet's disease; randomized single-blind control study (pilot study).

Davatchi F, Shams H, Rezaipoor M, Sadeghi-Abdollahi B, Shahram F, Nadji A, Chams-Davatchi C, Akhlaghi M, Faezi T, Naderi N.
Source

Behcet's Unit, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

BACKGROUND:
Ocular lesions, the main morbidity of Behcet's disease (BD), are the most difficult to treat. The aim of this study was to evaluate the efficacy of rituximab.

METHODS:
Inclusion criteria were retinal vasculitis and edema, resistant to cytotoxic drugs. Twenty patients were randomized to a rituximab group (RG) or cytotoxic combination therapy group (CCTG). Rituximab was given in two 1000-mg courses (15-day interval). Subjects received methotrexate (15 mg/weekly) with prednisolone (0.5 mg/kg per day). The CCTG received pulse cyclophosphamide (1000 mg/monthly), azathioprine (2-3 mg/kg per day) and prednisolone (0.5 mg/kg per day). The primary endpoint was the overall state of patients' eyes and the Total Adjusted Disease Activity Index (TADAI). Secondary endpoints were: visual acuity (VA), posterior uveitis (PU), and retinal vasculitis (RV). The baseline data were compared at 6 months by paired sample t-test and analysis of variance.

RESULTS:
TADAI improved significantly in the RG (t = 3.340, P = 0.009), but not in the CCTG (t = 2.241, P = 0.052). For secondary endpoints (RG/CCTG), the mean VA improved in two patients versus three (2/3), remained unchanged in 1/1, and worsened in 7/6 patients. The mean PU improved significantly in the RG (t = 3.943, P = 0.001), not in the CCTG (t = 2.371, P = 0.028). RV improved, but not statistically (t = 2.027, P = 0.057 vs. t = 1.045, P = 0.31). Edema of retina, disc and macula improved significantly in both, but much better for the RG (t = 2.781, P = 0.012 vs. t = 2.707, P = 0.014).

CONCLUSION:
Rituximab was efficient in severe ocular manifestations of BD, TADAI improved significantly after 6 months with rituximab, but not with CCT.

And one more study:

Treatment of retinal vasculitis in Behçet's disease with rituximab.

Sadreddini S, Noshad H, Molaeefard M, Noshad R.

Tabriz University of Medical Sciences, Golgasht St., Tabriz, Iran.

Abstract

Behçet's disease (BD) is more common in eastern than western countries. Physicians have frequently encountered problems in its treatment, especially eye involvement. Recurrent oral and genital aphthous ulcerations are the hallmarks of Behçet's disease but other organs can be involved and ocular disease is one of the most disabling manifestations. Up to now, there are some problems in treatment of the retinal vasculitis due to Behçet's disease. We reported one patient, with visual loss due to retinal vasculitis that was resistant to prednisolone and azathioprine. Our patient was treated successfully with rituximab and his remission was sustained for 24 months of follow-up. Rituximab is a chimeric monoclonal antibody that acts against the specific B cell antigen, CD20. The recent success of rituximab in autoimmune diseases, which is considered to be T cell-mediated, indicates that B cells must have a much broader role in the pathogenesis of autoimmune diseases than generally appreciated.

Behçet's is a rare disease, so very few studies are being done.

However, if you have disease that might be helped by Rituximab, my (slightly educated) guess is to try consume no milk, no dairy and no eggs for at least 4 weeks to see if it helps – it's worth a shot.

Rituximab and Ocrelizumab in Rheumatoid Arthritis and MS

One of the treatment stories was one we heard before in 2010 ISNI meeting in Sitges (SPAIN), the one about Rituximab and MS. Apart from the commercial history of Idec, Biogen, Genentech and so on, the important thing is that it all ended up in an phase II clinical trial. A revolutionary clinical trial.

It was revolutionary because it challenged the “MS-is-(for-sure)-a-T-cell-mediated-disease” dogma showing that a B cell therapy was able to achieve unbelivable results in MS. But most importantly it was revolutionary because it got a striking 91% reduction in new enhancing lessions compared to placebo and, despite being a phase II trial, achieved a 50% reduction in relapse rates compared to placebo in less than a year. These are Natalizumab-level results, but with a quite safer profile than Natalizumab. At least, the experience with other diseases yields a progressive multifocal leukoencephalopathy (PML) rate much lower to that of Natalizumab. Just 6 reumathoid arthritis (in which Rituximab is used routinely) patients have suffered PML over more than 120000 patients treated despite RA patients having used much more frequently concomitant immunessuppresants than MS patients do usually.

The results achieved in the study deserved a NEJM paper and, for sure, a phase III trial. But that won’t happen. At least not in the short term.

It turns out that Rituximab patent expires in the US in 2015. This means that, by the time the phase III is over, the patent will be over too. So, no profit then in doing such an investment. To surpass this inconvenience Genentech invented a new drug, antiCD20 as well, but humanized (Rituximab is chimeric), called Ocrelizumab, and started the whole process again. Then, obviously, we got a phase II trial with ocrelizumab in MS. Results have not been published yet but have been presented at 2010 ECTRIMS meeting and show,as expected, an almost equal efficacy profile to that of rituximab. But a patient died on the ocrelizumab arm from an unexpected “systemic inflammatory syndrome”. That could be chance and still hope larger studies to be assured… but it was not chance. Several rheumatoid arthritis trials with ocrelizumab have been terminated because “the overall benefit to risk profile of ocrelizumab was not favorable in RA” what it really means that 7 patients died unexpectedly in the high ocrelizumab dose arms of the trials.

(via ProHealth) 

"Study demonstrates that 95% of ME/CFS Patients have Anticardiolipin Antibodies, suggesting that ME/CFS may be an autoimmune condition"

A survey of the literature reports ACAs as commonserological markers in many different types of diseases,including viral diseases such as illnesses resulting fromchemical (1) and marine toxin exposure (4,5,6), HIV(7,8) and Epstein-Barr virus (9), hematological cancersincluding CLL and acute myelocytic leukemias, exposureto fungal organisms, malaria, and staphylococcusinfections (10,11), and autoimmune diseases such asmultiple sclerosis, systemic lupus erythematosus, autoimmunehepatitis, and more (2). This study demonstrates that a large percentage of patients clinically diagnosed with CFS have elevated levels of the IgM isotype to CL (95%), suggesting that CFS may be an autoimmune condition.As a possible autoimmune disease, CFS patients maybe treated by suppression of the ACA or by diminishingthe antigen CL in serum. Previous studies have shownthat treatment with monoclonal antibodies to B cellsreduces ACA levels to normal in patients with autoimmunedisease, leading to clinical improvements.

Specifically, Rituximab, a chimeric monoclonal CD20antibody, has been shown to normalize high ACAserum titers of patients with autoimmune systemic lupuserythematosus, rheumatoid arthritis, autoimmunethrombocytopenia, and autoimmune hemolytic anemia.Rituximab may serve as an effective therapeutic agentfor ameliorating the symptoms of CFS (11,13).

Therefore,classification of CFS as an autoimmune disordermay serve to increase the availability of treatmentoptions for patients suffering from the disease.

A study from 2009. Nice find, Dr. Speedy!

Rituximab Caveat

In my practice, rituximab at 375mg/m2 causes hypotension in most patients, about 60% need downward adjustment of their infusion rates and about 25% the hypotension is severe enough to be symptomatic. I would expect the hypotensive reactions to be more severe and frequent at the dose of 500mg/m2 used in the CFS protocol. If the patients signed a proper consent form they would have been warned that hypotension would be a risk, therefore most patients would be aware that they had received rituximab rather than placebo. The physicians who administered the rituximab would have to be adjusting the infusion rate in most patients and would also be aware that they had given the active drug rather than the placebo.

Therefore the statement that the study was double blinded is incorrect; it is not possible to double blind rituximab for the above reasons. Furthermore, the results are based on subjective, "how do I feel" criteria which could be influenced by the patients knowledge that they had received rituximab.

Interesting.

(As a side note: It is sad to see that Jamie always brings up XMRV)